Targeting pituitary adenomas with folate-conjugated multiple drug decorated liposomal formulations for improved antiproliferative anticancer efficacy

Abstract

In this work, we synthesized folate-conjugated dual-drug loaded double liposomes which are noted for their extremely high target specificity towards pituitary adenomas. It is known that while folate receptors are almost non-existent in normal tissues, they are overexpressed in non-functional pituitary adenomas. Synthesis, characterization and in vitro studies of folate-conjugated dual-drug loaded double liposomes for targeting non-functional pituitary adenomas is the highlight of this study. The size, zeta-potential, polydispersity index, in vitro release studies, stability of the nanoformulation, cytotoxicity and cellular uptake studies have been carried out. It was noted from the results that these are highly targeted liposomal formulation as expressed by the cellular uptake studies and are just sufficiently sized to escape the clearance mechanisms of body. They were also cytocompatible and were stable even after 60 days of shelf life with negligible changes in sizes, zeta potential as well as polydispersity index. The conjugation with folate particles resulted in the high specificity of the formulation to the specific targeted tissue as seen in cellular uptake by primary cell culture of non-functional pituitary adenomas. It may safely be concluded from the results that this approach may be a promising therapy for the future which has low cytotoxicity and high-specificity.

Keywords

• pituitary
• double liposomes
• adenomas
• folate
• conjugation